Neoadjuvant chemotherapy followed by minimally invasive esophagectomy
versus primary surgery for management of esophageal carcinoma: a
retrospective study
Author:
Yan Zheng,MD,PhD,1 Yin Li,MD,PhD,1, * Xianben Liu,MD, Ruixiang Zhang,MD,
Zongfei Wang,MD, Haibo Sun,MD, Shilei Liu,MD.
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou
University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P. R. China
Corresponding Author:
Li Yin, MD, PhD*
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou
University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P. R. China.
Tel.: +86 371 65587226
E-mail addresses: [email protected] (Yin Li)
1Yan Zheng, and 1Yin Li contributed equally to this article.
Authors’ contributions
Y. Z., and Y. L. had full access to all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis. Y. Z., X. L., R. Z., Z.
W., H. S., and S. L. contributed substantially to the study design, data analysis and
interpretation, and the writing of the manuscript. Y. Z., Y. L., Z. W., H. S., and S. L.
1
Neoadjuvant chemotherapy followed by minimally invasive esophagectomy
versus primary surgery for management of esophageal carcinoma: a
retrospective study
Abstract
There is no consensus about the combined therapeutic strategy for esophageal
squamous cell carcinoma in China. The quality control and standardization of surgery
procedures were far from satisfactory in past neoadjuvant chemotherapy trials, which
may underestimate the survival benefits. Therefore, we tried to evaluate the survival
benefit of paclitaxel plus platinum followed by minimally invasive esophagectomy
with total two-field lymphadenectomy patterns versus primary surgery. Between
06/2011 and 12/2014, there were 279 consecutive patients who underwent minimally
invasive esophagectomy with total two-field lymphadenectomy; 83 received
neoadjuvant chemotherapy and 196 primary surgery. Propensity score matching was
used to compare neoadjuvant chemotherapy patients and 76 matched primary surgery
patients. Effectiveness of neoadjuvant chemotherapy, adverse events, complications
after the operation, and survival rates were evaluated. After propensity score
matching, and compared with primary surgery, neoadjuvant chemotherapy was
significantly associated with a better survival (P = 0.049). The overall clinical
response rate of neoadjuvant chemotherapy was 77.1%. The pathological response
rate was 20.5%. There was no significant difference in complication rates between
two groups. Neoadjuvant chemotherapy with paclitaxel plus platinum followed by
minimally invasive esophagectomy and total two-field lymphadenectomy have better
2
OS over the primary surgery without serious adverse events.
Key Words: minimally invasive esophagectomy, neoadjuvant chemotherapy, survival
3
Background
More than 50% of worldwide esophageal squamous cell carcinoma (ESCC) patients
are located in China [1]. There is no consensus about the combined therapeutic
strategy for ESCC in China due to lack of randomized controlled trials (RCT).
Although the multidisciplinary therapeutic strategies have been explored for many
years in both western countries [2-7] and Japan [8], the treatment is quite different
from region to region based on the results of local RCTs.
The North American intergroup trial for ESCC (Radiation Therapy Oncology Group,
RTOG Trial 8911 or USA Intergroup 113) [2, 3] suggested that there was no survival
benefit from NAC for ESCC, whereas the Japan Clinical Oncology Group trial
(JCOG9907) [8] showed promising results for the same procedure. The survival
benefit of neoadjuvant chemotherapy (NAC) for ESCC remains controversial
worldwide [9, 10]. Due to contradictory evidence outside China and the lack of RCT
in China, we collected data from published articles and found the quality control of
surgical procedures in the RCTs was poor [11]. At that time, lymph node sampling
and transthoracic esophagectomy, transhiatal esophagectomy were acceptable in some
trials. Surgery was the only local control method that existed in the NAC strategy.
Different surgical procedures and ranges of lymphadenectomies may mask the
benefits of chemotherapy and significantly affect the survival rate.
In light of past RCTs [2-5, 8], we have designed a retrospective analysis in our
institute. The main concern of this study was to declare the survival benefit of NAC-
platinum plus paclitaxel (TP) over the primary surgery based on quality controlled
4
and standardized surgical procedure. Minimally invasive esophagectomy with total
two-field lymphadenectomy was the only used surgical procedure.
Methods
Inclusion criteria
The Ethics Review Committee of Henan Cancer Hospital/The affiliated Cancer
Hospital of ZhengZhou University approved this study officially. The approval
number is 2016ct081. Patients’ personal data were obtained. The consecutive patients
were retrospectively evaluated between 06/2011 and 12/2014. The inclusion criteria
were as follows: i) Thoracic ESCC; ii) Clinical staging T2-4aN0-2; iii) MIE with total
two-field lymphadenectomy; iv) With follow up, without clinical missing data. The
TNM Classification of Malignant Tumors 7th edition was adopted for the
clinicopathological profiles [12].
Neoadjuvant Chemotherapy
NAC comprised 2 cycles. Cisplatin or nedaplatin plus paclitaxel were repeated once
every 3 weeks. A dose of 175 mg/m2 paclitaxel was given by intravenous drip
infusion on days 1 and 8. Cisplatin or nedaplatin was administered at a dose of 75
mg/m2 by continuous infusion on days 2-4.
Surgical procedure
All patients received a right thoracolaparoscopic esophagectomy and at least 2-field
lymph node dissections. Cervical lymphadenectomy was performed when suspicious
lymph node metastasis was reported on a color ultrasound. First, the patient was
placed in a left semi-prone-position. The thoracic esophagus was mobilized and the
5
lymph nodes were dissected. The regional lymph nodes included the mediastinal
lymph nodes (left recurrent laryngeal never, right recurrent laryngeal nerve,
paraesophageal, paratracheal, subcarinal, supradiaphragmatic and posterior
mediastinal lymph nodes). Then the position was modified to a supine position. A 2-3
cm left cervical incision was made. Muscle sparing methods and blunt dissection were
used to expose the cervical esophagus. In the abdominal part, laparoscope was used
for gastric mobilization. A 3-cm gastric tube was made with linear staplers (TLC,
Ethicon, USA) and perigastric lymph nodes (celiac, left gastric artery, common
hepatic artery and splenic artery lymph nodes were dissected. Finally, the gastric
conduit was delivered to the neck to be sewn with the distal esophagus by using a
hand-sewn 3 layered anastomosis (Li's anastomosis) [13]. Figure 1 showed the
standard extent of lymph nodes dissection.
Clinical and Pathological Tumor Effects
Preoperational investigations included esophagography, esophageal endoscopic
ultrasound, esophagoscopy, contrast-enhanced thoracic CT scan, abdominal
ultrasound, brain MRI, cervical color ultrasound, and Emission Computed
Tomography (ECT). If a patient accepted, positron emission tomography-CT
(PET/CT) would be adopted instead of chest CT, abdominal ultrasound, cervical color
ultrasound and ECT. No patients have repeated PET scan and endoscopy after
induction. The Response Evaluation Criteria in the Solid Tumors [14] were used to
evaluate the clinical tumor responses. Radiographic criteria for positive lymph nodes
was that the shortest diameter of lymph nodes > 1 cm and the ratio of long axis >
6
0.65, The pathological complete response (pCR) was defined as no evident viable
cancer cells [15]. Common Terminology Criteria for Adverse Events (CTCAE)
Version 3.0 [16] was adopted to assess the adverse events of NAC.
Follow-Up
All patients were followed at outpatient clinics or contacted by a research nurse by
phone. Over the first 3 years, the patients received clinical and radiological evaluation
every 3 months. For the next 2 years, the patients were examined every 6 months.
After 5 years, the patients were followed annually until death. The surveillance
studies after surgery included chest CT scans, abdominal and cervical ultrasound.
PET/CT, abdominal CT scan, endoscopy, brain MRI and ECT were performed
depending on the patient’s status.
Statistical Analysis
The SPSS 23.0 software for Windows (SPSS, Chicago, IL, USA) was used to perform
the statistical analysis. The propensity score (PS) matched analysis was used to reduce
the bias. PS was calculated to fit with variables, including age, sex, length of tumor,
location of tumor, clinical T stage, clinical N stage and clinical TNM stage. The
characteristics and pre-therapy data between the groups were compared using
Student’s t-test for all quantitative data and both a chi-square test and a Mann-
Whitney U test for qualitative data. Categorical variables were compared by Fisher’s
exact test. The Kaplan-Meier method was adopted to analyze overall survival (OS)
with a log-rank test. We reported survival rates and Hazard ratios with 95%
confidence intervals (CIs). The OS was defined as the time from the operation in the
7
surgery group and the first date of NAC to the death or most recent follow-up. A two-
sided P value of 0.05 was defined as statistically significant.
Results
Patient Characteristics
Between 06/2011 and 12/2014, there were 279 consecutive patients who meet the
criterion; 83 received NAC and 196 primary surgery. After PS matched analysis, there
were 76 matched primary surgery patients (Figure 3). The characteristics of the 159
patients after PS matching were summarized in Table 1. The primary data was
comparable. The NAC group had much earlier pathological stage (P<0.001).
Clinical Effect of Neoadjuvant Chemotherapy
CR to NAC were observed in 16 (19.3%) patients, partial responses (PR) in 48
(57.8%) patients, SD in 17 (20.5%), and progressive disease (PD) in 2 (2.4%).
Therefore, the overall clinical response rate was 77.1%. During the same period, there
were 6 excluded NAC patients. One patient after NAC (clinical effect, stable disease,
SD) underwent R1 resection because of the invasion of aorta. Five patients didn’t
received surgery after NAC; three got progressive disease (PD) clinically and
underwent definitive chemoradiotherapy. Two got clinical complete response (CR)
after NAC, refused to do surgery and accepted definitive chemoradiotherapy.
Toxicity of Neoadjuvant Chemotherapy
Most of the patients received 2 cycles of NAC (86.7%). Paclitaxel + NDP were the
most adopted chemotherapy regimen (55.4%). Table 2 showed the toxicity of NAC.
One (1.2%) patient had grade 4 leukopenia, 8 (9.6%) had grade 3 leukopenia, and 33
8
(39.8%) had grade 1 leukopenia. None of the patients had grade 4; hepatorenal and
gastrointestinal toxicity. Only 3 patients adjusted the dose because of side effects.
Surgical Outcomes and Pathological Effects
The surgical data were shown in Table 3. There was no significantly difference
between the groups. Table 4 showed the clinical response to NAC. Based on RECIST
1.0[14], 19.3% of patients had CR, 57.8% had PR, 20.5% had SD and 2.4% had PD.
The pathological response rate (pCR) was 20.5%.
Survival
The median follow-up for all of the patients was 36 months (ranging from 6 to 68).
Figure 2 described the OS of patients between the two groups with the Kaplan-Meier
method, and a log-rank test was used. The five-year estimated OS rates for the NAC
group and surgery group were 71.7% and 45.3%, respectively. The mean survival
time for the NAC group was 54.359 months (log-rank, 95% CI, 50.417 to 58.301).
The mean survival period was 49.353 months for the primary surgery group (log-rank,
95% CI, 43.770 to 54.936). The estimate median survival time for surgery group was
51 months. However, the median survival time for the NAC group has not yet been
reached. Seventeen pCR patients were all alive. Only one of them had recurrence in
lung in 56 months after the first day of NAC.
Discussion
Our study demonstrated that NAC with TP followed by MIE with total two-field
lymphadenectomy improved OS comparing with primary surgery. There are 2
possible reasons for the better NAC results. First, NAC-TP got a high clinical (77.1%)
9
and pathological (20.5%) response rate. Second, the standarlized two-field
lymphadenectomy MIE. In a study assessing the outcome of NACR followed by
surgery, en bloc esophagectomy was compared with a transhiatal esophagectomy. The
more radical surgery was an independently better survival factor, regardless of the
response to NACR [17]. Another study on NACR for patients with ESCC showed that
the degree of lymph node dissection significantly influenced the OS [18]. Compared
with NACR, NAC didn’t have the effect for local control. The quality of the operation
was more important in NAC than NACR for EC [19]. In the 3 large multicenter
clinical trials on NAC, too little attention was given to standardize the surgical
procedure [19]. All the cases included in our study represent the results of a single
surgeon's experience. That was easy to standardize surgical procedure.
The side effects toxicity of TP-NAC was tolerable. Hepatorenal disorder (grade 1)
was the most common side effect (44.6%) in the present study. Only 1 (1.2%) patient
had Grade 4 bone marrow depression. The vomiting and stomatitis were another
common side effect, occurring in 4.8% of the patients (4 cases). The adverse effects of
weekly paclitaxel and a 21-day cycle of cisplatin were mild. Due to the overall mild
non-hematological and hematological toxicities, the weekly TP regimen was tolerable
for many patients.
Esophageal surgery is usually associated with a high postoperative morbidity and
mortality. However, our data shown the postoperative mortality was zero. After NAC,
the incidence of postoperative morbidity and mortality has not increased among
patients compared to patients treated by primary surgery. There was no significant
10
difference in complication rate between two groups. MIE after NAC was safe.
The rates of pCR in patients treated with NAC ranged from 2% to 17% in previous
reports of this combined strategy [11], whereas we achieved a pCR rate of 20.5% for
primary tumors and the lymph nodes, which was relatively high. In previously
reports, NACR could achieve a 20%-40% pCRT rate. The high pCR rate might be
explained by the fact that the TP regime was adopted in this study, whereas in the past
CF was mostly adopted. More and more studies have reported that paclitaxel cell
toxicity is effective for treating squamous cell carcinoma (SCC) [20]. Based on the
retrospective data and clinical experience, weekly paclitaxel was tolerable, might have
been related to the high pCR rate. As a retrospective study, there must be some
selection bias, which may also contributed to the high pCR rate. That was also the
reason why we wanted to start a RCT.
The ESCC mostly occurs in less-developed regions of the world. More than 50% of
the ESCC cases were located in China (53%, 210 000 cases) [1]. Henan province
carried the highest burden of ESCC in China [21]. Based on huge patient number, in
light of past trials and the results of our studies, we designed the multicenter RCT in
China[22]. Compared with past trials, we emphasized standard surgical procedures
and a standard range of lymphadenectomy. The recruitment of 528 cases will be done
within 2.5 years ClinicalTrials.gov Identifier: NCT02395705. Hopefully, it will
provide a conclusion for the using of NAC with total two-field lymphadenectomy for
ESCC.
Conclusions
11
NAC with TP followed by MIE with total two-field lymphadenectomy is better than
primary surgery in terms of OS without additional serious adverse events. This
combined therapy might be a highly recommended treatment modality for patients
with stage II/III ESCC.
Acknowledgement
This project was supported by the Henan provincial public health authority (Grant
Number. 201501003).
This project was supported by Henan province ministry of education (Grant
Number.17A320048) .
This project was supported by Wu Jieping fund (Grant Number. 320.6799.15062 and
320.2730.1892).
Ethics approval
The study was approved by the Henan Cancer Hospital Ethics Committee, approval
number: 2016ct081
Competing interests
The authors declare that they have no competing interests.
12
References
1. Siegel R, Desantis C, Jemal A: Colorectal cancer statistics, 2014. CA: a cancer
journal for clinicians 2014, 64(2):104-117.
2. Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes
N, Haller DG, Ajani J, Kocha W et al: Chemotherapy followed by surgery
compared with surgery alone for localized esophageal cancer. The New
England journal of medicine 1998, 339(27):1979-1984.
3. Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani
JA, Kocha W, Minsky BD, Roth JA et al: Long-term results of RTOG trial 8911
(USA Intergroup 113): a random assignment trial comparison of
chemotherapy followed by surgery compared with surgery alone for
esophageal cancer. Journal of clinical oncology : official journal of the
American Society of Clinical Oncology 2007, 25(24):3719-3725.
4. Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE: Long-term results of
a randomized trial of surgery with or without preoperative chemotherapy in
esophageal cancer. Journal of clinical oncology : official journal of the
American Society of Clinical Oncology 2009, 27(30):5062-5067.
5. Medical Research Council Oesophageal Cancer Working G: Surgical resection
with or without preoperative chemotherapy in oesophageal cancer: a
randomised controlled trial. Lancet 2002, 359(9319):1727-1733.
6. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge
Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA,
13
Bonenkamp JJ et al: Preoperative chemoradiotherapy for esophageal or
junctional cancer. The New England journal of medicine 2012, 366(22):2074-
2084.
7. Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W,
Watanabe H, Isono K, Aoyama N et al: Surgery plus chemotherapy compared
with surgery alone for localized squamous cell carcinoma of the thoracic
esophagus: a Japan Clinical Oncology Group Study--JCOG9204. Journal of
clinical oncology : official journal of the American Society of Clinical Oncology
2003, 21(24):4592-4596.
8. Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T,
Yabusaki H, Aoyama N, Kurita A et al: A randomized trial comparing
postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil
versus preoperative chemotherapy for localized advanced squamous cell
carcinoma of the thoracic esophagus (JCOG9907). Annals of surgical
oncology 2012, 19(1):68-74.
9. Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J: Survival
benefits from neoadjuvant chemoradiotherapy or chemotherapy in
oesophageal carcinoma: a meta-analysis. The Lancet Oncology 2007,
8(3):226-234.
10. Kumagai K, Rouvelas I, Tsai JA, Mariosa D, Klevebro F, Lindblad M, Ye W,
Lundell L, Nilsson M: Meta-analysis of postoperative morbidity and
perioperative mortality in patients receiving neoadjuvant chemotherapy or
14
chemoradiotherapy for resectable oesophageal and gastro-oesophageal
junctional cancers. The British journal of surgery 2014, 101(4):321-338.
11. Zheng Y, Li Y, Liu X, Sun H, Wang Z, Zhang R: Reevaluation of Neoadjuvant
Chemotherapy for Esophageal Squamous Cell Carcinoma: A Meta-Analysis
of Randomized Controlled Trials Over the Past 20 Years. Medicine 2015,
94(27):e1102.
12. Rice TW, Blackstone EH, Rusch VW: 7th edition of the AJCC Cancer Staging
Manual: esophagus and esophagogastric junction. Annals of surgical
oncology 2010, 17(7):1721-1724.
13. Zheng Y, Li Y, Wang Z, Sun H, Zhang R: A video demonstration of the Li's
anastomosis-the key part of the "non-tube no fasting" fast track program
for resectable esophageal carcinoma. Journal of thoracic disease 2015,
7(7):1264-1268.
14. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey
J, Arbuck S, Gwyther S, Mooney M et al: New response evaluation criteria in
solid tumours: revised RECIST guideline (version 1.1). European journal of
cancer (Oxford, England : 1990) 2009, 45(2):228-247.
15. Davies AR, Gossage JA, Zylstra J, Mattsson F, Lagergren J, Maisey N, Smyth EC,
Cunningham D, Allum WH, Mason RC: Tumor stage after neoadjuvant
chemotherapy determines survival after surgery for adenocarcinoma of the
esophagus and esophagogastric junction. Journal of clinical oncology : official
journal of the American Society of Clinical Oncology 2014, 32(27):2983-2990.
15
16. Kaplan DK, Whyte RI, Donnelly RJ: Oesophagogastrectomy using stapling
instruments. European journal of cardio-thoracic surgery : official journal of
the European Association for Cardio-thoracic Surgery 1988, 2(2):95-99.
17. Rizzetto C, DeMeester SR, Hagen JA, Peyre CG, Lipham JC, DeMeester TR: En
bloc esophagectomy reduces local recurrence and improves survival
compared with transhiatal resection after neoadjuvant therapy for
esophageal adenocarcinoma. The Journal of thoracic and cardiovascular
surgery 2008, 135(6):1228-1236.
18. Chao YK, Liu HP, Hsieh MJ, Wu YC, Liu YH, Yeh CH, Chang HK, Tseng CK: Lymph
node dissection after chemoradiation in esophageal cancer: a subgroup
analysis of patients with and without pathological response. Annals of
surgical oncology 2012, 19(11):3500-3505.
19. Markar SR, Wiggins T, Ni M, Steyerberg EW, Van Lanschot JJ, Sasako M, Hanna
GB: Assessment of the quality of surgery within randomised controlled trials
for the treatment of gastro-oesophageal cancer: a systematic review. The
Lancet Oncology 2015, 16(1):e23-31.
20. Hashiguchi T, Nasu M, Hashimoto T, Kuniyasu T, Inoue H, Sakai N, Ouchi K,
Amano T, Isayama F, Tomita N et al: Docetaxel, cisplatin and 5-fluorouracil
adjuvant chemotherapy following three-field lymph node dissection for
stage II/III N1, 2 esophageal cancer. Molecular and clinical oncology 2014,
2(5):719-724.
21. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J:
16
Cancer statistics in China, 2015. CA: a cancer journal for clinicians 2016,
66(2):115-132.
22. Zheng Y, Li Y, Liu X, Zhang R, Wang Z, Sun H, Liu S: A phase III, multicenter
randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus
cisplatin versus surgery alone for stage IIA-IIIB esophageal squamous cell
carcinoma. Journal of thoracic disease 2017, 9(1):200-204.
Figure legend
Figure 1. The graph of standard lymph node dissection. (A) and (B) exposure of the
left recurrent laryngeal nerve (RLN). The lymph nodes from thyroid gland and the
LNs along the left RLN were removed using endoscopic scissors; (C) The region of
lymph nodes dissection along the right recurrent laryngeal nerve (RLN); (D) The
region of lymph nodes dissection in abdominal cavity.
Figure 2. Kaplan-Meier survival analysis of ESCC patients (n = 159). The survival
rate of patients in the NAC group was higher than patients in the surgery alone group
(log-rank test, P = 0.049).
Figure 3. Between 06/2011 and 12/2014, there were 279 consecutive patients who
meet the criterion; 83 received NAC and 196 primary surgery. After PS matched
analysis, there were 76 matched primary surgery patients. Finally, there were 159
patients included in this study. ESCC, esophageal squamous cell carcinoma; NAC,
neoadjuvant chemotherapy; PS, propensity score.
17
Table 1. Characteristics and pre-therapy data of patients with ESCC after and before the propensity score matching
Characteristics Number
(%)
Different strategy
S (n=76) NAC+S (n=83) χ2/F p Value
Characteristics and pre-therapy data of patients with ESCC after the propensity score matching in 159 patients
Age Y(Mean±SD) 60.47±0.973 60.6±0.824 2.719 0.101
Range 40-74 42-81
Gender N(%) 0.003 0.955
Male 130(81.8) 62(81.6) 68(81.9)
Female 29(18.2) 14(18.4) 15(18.1)
Location N(%) 2.476 0.290
Upper thoracic 35(22.0) 15(19.7) 20(24.1)
Middle thoracic 71(44.7) 31(40.8) 40(48.2)
Lower thoracic 53(33.3) 30(39.5) 23(27.7)
Clinical TNM staging 7th ed N(%) 0.297 0.586
19
cStageⅡ 78(49.1) 39(51.3) 39(47.0)
cStageⅢ 81(50.9) 37(48.7) 44(53.0)
Adjuvant therapy <0.001 0.982
Yes 94(59.1) 45(59.2) 49(59.0)
No 65(40.9) 31(40.8) 34(41.0)
Adjuvant radiation 0.202 0.653
Yes 19(11.9) 10(13.2) 9(10.8)
No 140(88.1) 66(86.8) 74(89.2)
Pathological TNM staging 7th ed N(%) <0.001 a
pCR 17(10.7) NA 17(20.5)
I 14 (8.8) 6(7.9) 8(9.6)
II 74 (46.5) 42(55.3) 32(38.6)
III 53 (33.3) 27(35.5) 26(31.3)
IV 1 (0.6) 1(1.3) 0
20
ESCC, esophagus squamous cell carcinoma; Y, years; N, number; c, clinical; TNM, pathological tumor/node/metastasis; NAC, neo adjuvant
chemotherapy; S, surgery; a Fisher exact test Statistically significant (p < 0.05); pCR, pathological complete response; b Statistically significant (p
< 0.05)
21
Table 2. Side effects of NAC
Toxicity Grade 0
N(%)
Grade 1
N(%)
Grade 2
N(%)
Grade 3
N(%)
Grade 4
N(%)
Leukopenia 39(47) 33(39.8) 8(9.6) 2(2.4) 1(1.2)
Gastrointestinal
symptoms
37(44.6) 31(37.3) 11(13.3) 4(4.8) 0
Hepatorenal disorder 43(51.8) 37(44.6) 3(3.6) 0 0
a, Common Terminology Criteria for Adverse Events Version 3.0; N, number.
22
Table 3. Operation data for both groups
Variable NAC+S
(n=83)
S
(n=76)
p Value
Operation time(minutes), Mean±SD 227.94±39.57 239.74±47.293 0.089
EBL (ml), median (range) 100 (50-400) 70 (30-400) 0.093
Total nodes collected, median (range) 16 (15-69) 16 (15-42) 0.608
Pathologically positive lymph nodes, median
(range)
0(0-28) 0(0-9) 0.582
Postoperative days, median (range) 9 (5-30) 8 (5-32) 0.052
Hospital mortality, (%) 0 0 NA
Complication, N (%) 20(24.1) 19(25.0) 0.895
Pneumonia 11(13.3) 9(11.8) 0.789
Arrhythmia 7(8.4) 6(7.9) 0.901
Anastomotic leakage 2(2.4) 1(1.3) >0.99
Incision infection 4(4.8) 2(2.6) 0.759
Recurrent laryngeal nerve injury 16(19.3) 13(17.1) 0.723
Chylothorax 0 1(1.3) 0.478
23
NAC, neoadjuvant chemotherapy; S, surgery; EBL, estimated blood loss; N, number; NA, not applicable; a Statistically significant (p < 0.05).
24
Table 4. Response evaluation of the patients with ESCC to NAC
Characteristics Variable Absolute value
(%)
Radiologic
response
CR 16(19.3)
PR 48(57.8)
SD 17(20.5)
PD 2(2.4)
Pathologic
response
CR 17(20.5)
other 66(79.5)
Down staging Yes 33(39.8)
No 50(60.2)
ESCC, esophagus squamous cell carcinoma; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.
25